Synthesis and Properties of Substituted Isoxazolo[3',4':4,5]thieno[2,3-b]pyridines

We synthesized derivatives of a novel heterocyclic system, isoxazolo[3',4':4,5]thieno[2,3-b]pyridine by sequential conversions in three steps: isomerization of 2-(2-R-ethylthio-2-oxo)-3-pyridyl cyanides obtained by alkylation from substituted 3-cyano-2(1H)-pyridinethiones by -halomethyl ketones in alkaline medium, to form 3-aminothieno[2,3-b]pyridines; diazotization of the amino group followed by nucleophilic substitution of the diazonium group by an azido group, bypassing the step of isolating the diazonium salts; and thermolysis of the azides formed.     

Synthesis and transformations of 3-(1H-pyrrol-1-yl)thieno[2,3-b]pyridines

Reactions of 2,5-dimethoxytetrahydrofuran with 3-aminothieno[2,3-b]pyridines afford a number of substituted 3-(1H-pyrrol-1-yl)thieno[2,3-b]pyridines. The possibility of the reaction and the yield of the product are determined by the character of a substituent in position 2 of thieno[2,3-b]pyridine. The Curtius rearrangement of 2-acylazido-3(1H-pyrrol-1-yl)thieno[2,3-b]pyridines yields 4,5-dihydropyrido[3",2":4,5]thieno[2,3-e]pyrrolo[1,2-a]pyrazin-4-ones. The molecular and crystal structures of ethyl 4-methoxymethyl-6-methyl-3-(1H-pyrrol-1-yl)thieno[2,3-b]pyridine-2-carboxylate were determined by X-ray diffraction analysis.     

Synthesis of substituted 2-amino-3-cyano-7,9-dimethyl-4H-pyrano[2",3":4,5]thieno[2,3-b]pyridines

4,6-Dimethyl-2H-thieno[2,3-b]pyridin-3-one reacts with 2-aryl-1,1-dicyanoethylenes or an aromatic aldehyde/ketone (cyclohexanone and piperidone derivatives) and malononitrile to give substituted 2-amino-3-cyano-7,9-dimethyl-4H-pyrano[2",3":4,5]thieno[2,3-b]pyridines.     

Synthesis and Properties of Derivatives of the new Heterocyclic System Benz[4,5]imidazo[1,2-c]pyrido[3',2';4,5]thieno[2,3-e]pyrimidine

Derivatives of a new heterocyclic system - benz[4,5]imidazo[1,2-c]pyrido[3',2';4,5]thieno[2,3-e]pyrimidine have been obtained by successive reactions in three stages - alkylation of 3-cyanopyridine-2(1H)-thiones with 2-chloromethylbenzylimidazole to give 2-benzimidazolylmethylthio-3-cyanopyridines, closing the thiophene ring in the latter to form 3-amino-2-(benzimidazolyl-2)thieno[2,3-b]pyridines, and cyclization of the pyrimidine ring by acylation with carboxylic acid anhydrides or chlorides.     

Synthesis and properties of (thieno[2,3-<Emphasis Type="Italic">b</Emphasis>]pyridin-3-yl)iminotriphenylphosphoranes. Molecular structure of (2-benzoyl-4-methoxymethyl-6-methylthieno[2,3-<Emphasis Type="Italic">b</Emphasis>]pyridin-3-yl)iminotriphenylphosphorane

Iminophosphoranes containing a thieno[2,3-b]pyridine fragment were obtained through a sequence of reactions: 1) alkylation of 3-cyano-2(1H)-pyridinethiones in alkaline medium by an -halocarbonyl compound with subsequent Thorpe-Ziegler cyclization of the resultant 2-thioalkylpyridines to give 3-aminothieno[2,3-b]pyridines, 2) diazotization of the amino group and nucleophilic substitution of the diazonium group by an azido group without isolation of the diazonium salts, and 3) reaction of the 3-azidothieno[2,3-b]pyridines with triphenylphosphine.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1853–1862, December, 2004.     

3-Cyanopyridine-2(1H)-thiones and 3-cyano-2-(methylthio)pyridines in the synthesis of substituted 3-(aminomethyl)pyridines

The reactions of substituted 3-cyanopyridine-2(1H)-thiones and 3-cyano-2-(methylthio)pyridines with lithium aluminum hydride in anhydrous diethyl ether afforded the corresponding 3-aminomethyl derivatives, which were used in the synthesis of the corresponding amides.     

New Cu(II), Co(II), and Ni(II) complexes with thieno[2,3-b]pyridine and 2-methylthieno[2,3-b]pyridine as ligands: Synthesis and crystal structures

Although thienopyridines attract attention because of their biological activities, they have not been used as ligands in coordination compounds. Thieno[2,3-b]pyridine was prepared by known procedures; by reduction of 2-nitrothiophene, and reaction of the resulting 2-thienyl ammonium salt with malondialdehyde tetramethylacetal in the presence of zinc chloride. The same procedure was used for the preparation of a new derivative, 2-methylthieno[2,3-b]pyridine, starting from 2-methyl-5-nitrothiophene. The thienopyridines were used in the synthesis of coordination compounds. Chlorides, isothiocyanates, acetates, and chloroacetates of copper(II), nickel(II), or cobalt(II) were used as starting salts. The prepared complexes were characterized by elemental analysis and FT IR. Structures of the four complexes were determined by single-crystal X-ray diffraction analysis. Presented at the 1st International Conference “Applied Natural Sciences” on the occasion of the 10th anniversary of the University of Ss. Cyril and Methodius, Trnava, 7–9 November 2007.     

Intramolecular 4+2 cycloaddition of thieno[2,3-e][1,2,4]triazines: routes towards condensed thieno[2,3-b]pyridines

Synthetic approaches towards new condensed thienopyridine ring systems including furo[2,3-b]thieno[3,2-e]pyridines, bisthieno[2,3-b:3′,2′-e]pyridines, 5H-chromeno[2,3-b]thieno[3,2-e]pyridines, 5H-benzo(f)chromeno[2,3-b]thieno[3,2-e]pyridines have been achieved by application of intramolecular 4+2 cycloaddition reactions of suitably designed thieno[2,3-e][1,2,4]triazines tethered with alkene or alkyne terminals.     

Alkylation of 6-(3-Indolyl)indolo[2,3-b]carbazole

The methylation and allylation of 6-(3-indolyl)indolo[2,3-b]carbazole were studied, and its trimethyl and mono-, di-, and triallyl derivatives were obtained.     

Derivatives of condensed thieno[2,3-d]-pyrimidines. 20. Synthesis of 2-substituted 5,6-dihydro-8H-pyrano[4′,3′:4,5]thieno[2,3-d]pyrimidin-4(3H)-ones and 5,6,7,8-tetrahydrobenzo-[b]thieno[2,3-d]pyrimidin-4-ones

We have developed a method for obtaining 2-substituted 3-amino-6,6-dimethyl-5,6-dihydro-8H-pyrano[4′,3′:4,5]-and 5,6,7,8-tetrahydrobenzo[b]thieno[2,3-d]pyrimidin-4(3H)-ones, converted by deamination to the corresponding dihydropyranothieno-3H-pyrimidinones. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 441–444, March, 2006.     

Synthesis of 3-amino-4-methyl-6-trifluoromethylthieno[2,3-b]pyridine-2-carboxanilide and its crystal and molecular structure

4-Methoxy-1,1,1-trifluoropent-3-en-2-one reacts with cyanothioacetamide to give 3-cyano-4-methyl-6-trifluoromethylpyridine-2(1H)-thione, which was transformed into 3-amino-4-methyl-6-trifluoromethylthieno[2,3-b]pyridine-2-carboxanilide by the reaction with chloroacetanilide. The crystal and molecular structure of the amide obtained was studied by X-ray analysis. Translated fromIzvestiya Akademii Nauk Seriya Khimicheskaya, No. 4, pp. 701–703, April, 1998.     

Synthesis of 2,3-Dihydroimidazo[1,2-a]pyridines from 1,3-Diketones

A series of 2-hydroxy-, 2-chloro-, and 2-(2-hydroxyethylamino)-6-aryl-4-polyfluoroalkyl-3-cyanopyridines has been synthesized. The latter react with phosphorus oxychloride to give fluorine containing 2,3-dihydroimidazo[1,2-a]pyridines.     

Synthesis and reactivity of thieno[2,3-<Emphasis Type="Italic">b</Emphasis>]pyridine-2,3-diamines

It has been established that the interaction of N¹-(2-hydroxyphenylmethylthieno[2,3-b]pyrid-3-yl)arylamides with hydrazine hydrate leads to thieno[2,3-b]pyridine-2,3-diamines. It was shown that the reaction of the latter with acetylacetone and acetoacetic ester occurs regioselectively at the amino group in position 3 of the thiophene ring. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1400–1408, September, 2007.     

Interaction of 3-amino-2-(isoxazol-3-yl)-4-methoxymethyl-6-methyl-thieno[2,3-<Emphasis Type="Italic">b</Emphasis>]pyridine with Raney nickel

3-Amino-2-(isoxazol-3-yl)-4-methoxymethyl-6-methylthieno[2,3-b]pyridine was synthesized by the reaction of 2(1H)-thioxopyridine-3-carbonitrile with 3-chloromethylisoxazole in the presence of two equivalents of KOH. Boiling of 3-amino-2-(isoxazol-3-yl)-4-methoxymethyl-6-meth-ylthieno[2,3-b]pyridine with Raney nickel results in 4-aminothieno[2,3-b;4,5-b′]dipyridine or 5-(4-amino-2-pyridyl)pyridine depending on the reaction conditions. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 669–670, March, 2008.     

Studies on the Synthesis of New 3-(3,5-Diamino-1-substituted-pyrazol-4-yl)azo-thieno[2,3-b]pyridines and 3-(2-Amino-5,7-disubstituted-pyrazolo[1,5-a]pyrimidine-3-yl)azothieno[2,3-b]pyridines

Coupling the diazonium salt of 3-amino-2-cyano-4,6-dimethylthieno[2,3-b]pyridine 1 with malononitrile 2 gave 2-cyano-3-(hydrazonomalononitrile)-4,6-dimethylthieno[2,3-b]pyridine 3 which then reacted with hydrazine compounds 4a-4h to yield corresponding 2-cyano-3-(3,5-diamino-1-substituted-pyrazol-4-yl)azo-4,6-dimethylthieno[2,3-b]pyridines 5a-5h. The 2-cyano-3-(2-amino-5,7-disubstituted-pyrazolo-[1,5-a]pyrimidine-3-yl)azo-4,6-dimethylthieno[2,3-b]pyridines 7a-7f were obtained in good yield by the cyclocondensation reaction of 2-cyano-3-(3,5-diamino-pyrazol-4-yl)azo-4,6-dimethylthieno[2,3-b]pyridine 5a with the appropriate 1,3-diketones 6a-6f under acidic condition.     

Synthesis of Derivatives of 3-Cyano-6-methyl-5-phenylcarbamoylpyridine-2(1H)-thione and 3-Cyano-6-methyl-5-phenyl-carbamoylpyridine-2(1H)-selenone

The reaction of ethoxymethylenacetylacetanilide with cyanothioacetamide or cyanoselenoacetamide in the presence of N-methylmorpholine and alkylating agents gave substituted 2-alkylthio- and 2-alkylselenopyridines and thieno[2,3-b]pyridines.     

Reaction of 6-methoxybenzo[b]furan-3(2H)-one and benzo[b]thiophen-3(2H)-one with 2-aryl-1,1-dicyanoethylenes as a convenient synthetic route to substituted 2-amino-4-aryl-1,3-dicyano-7-methoxydibenzo[b,d]furans and 2-amino-4-aryl-3-cyano-4H-benzothieno[3,2-b]pyrans

The reactions of 6-methoxybenzo[b]furan-3(2H)-one with 2-aryl-1,1-dicyanoethylenes and malononitrile or with aromatic aldehyde and two moles of malononitrile afford 2-amino-4-aryl-1,3-dicyano-7-methoxydibenzo[b,d]furans. The reactions of benzo[b]thiophen-3(2H)-one with 2-aryl-1,1-dicyanoethylenes or with aromatic aldehyde and one mole of malononitrile produce 2-amino-4-aryl-3-cyano-4H-benzothieno[3,2-b]pyrans.